Anoikis molecular pathways and its role in cancer progression

Biochim Biophys Acta. 2013 Dec;1833(12):3481-3498. doi: 10.1016/j.bbamcr.2013.06.026. Epub 2013 Jul 2.


Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonizing of distant organs. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are vital steps during cancer progression and metastatic colonization, the ability of cancer cells to resist anoikis has now attracted main attention from the scientific community. Cancer cells develop anoikis resistance due to several mechanisms, including change in integrins' repertoire allowing them to grow in different niches, activation of a plethora of inside-out pro-survival signals as over-activation of receptors due to sustained autocrine loops, oncogene activation, growth factor receptor overexpression, or mutation/upregulation of key enzymes involved in integrin or growth factor receptor signaling. In addition, tumor microenvironment has also been acknowledged to contribute to anoikis resistance of bystander cancer cells, by modulating matrix stiffness, enhancing oxidative stress, producing pro-survival soluble factors, triggering epithelial-mesenchymal transition and self-renewal ability, as well as leading to metabolic deregulations of cancer cells. All these events help cancer cells to inhibit the apoptosis machinery and sustain pro-survival signals after detachment, counteracting anoikis and constituting promising targets for anti-metastatic pharmacological therapy. This article is part of a Special Section entitled: Cell Death Pathways.

Keywords: AMP activated protein kinase; AMPK; Anoikis; Cancer; ECM; EGFR; EMT; ERK; FAK; FLICE inhibitory protein; FLIP; GSK-3; HGF; HIF; IKK; IL; ILK; IκB kinase; MAPK; MET; MMP; Mcl-1; Metabolism; MicroRNA; NADPH oxidase; NFκB; Nox; OMM; PDGFR; PDK; PERK; PI3K; PIP3; PK-M2; PKB; PPP; PTEN; ROS; RTKs; Reactive oxygen species; SMA; TNFR; TrkB; VEGFR; epidermal growth factor receptor; epithelial–mesenchymal transition; extracellular matrix; extracellular signal-regulated kinase; focal adhesion kinase; glycogen synthase kinase-3; hepatocyte growth factor; hypoxia-inducible factor; integrin-linked kinase; interleukin; mesenchymal epithelial transition; metalloproteinase; mitogen activated protein kinase; myeloid cell leukemia sequence 1; nuclear factor-κB; outer mitochondrial membrane; pentose phosphate pathway; phosphatase and tensin homolog; phosphatidylinositol 3,4,5-triphosphate; phosphoinositide-3-OH kinase; platelet-derived growth factor receptor; protein kinase B; protein kinase like endoplasmic reticulum kinase; pyruvate dehydrogenase kinase; pyruvate kinase isoform-2; reactive oxygen species; receptor tyrosine kinases; tumor necrosis factor receptor; tyrosine kinase receptor B; vascular endothelial growth factor receptor; α-smooth muscle actin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anoikis*
  • Cytoprotection
  • Disease Progression*
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / pathology*
  • Signal Transduction*